Inflammation blockade improves pancreatic islet function

Abstract 

Pancreatic islet transplantation can replace insulin-secreting β cells in patients with diabetes mellitus. However, current methodology for isolating islets from a pancreas only retrieves a portion of the total islets. Within these limited number of islets, nearly 50% of β cells lose biological function before transplantation. Protecting and improving β-cell viability and function was the goal of this study. Previously we observed that an anti-inflammatory compound, lisofylline (LSF), protects β cells from cytotoxicity during diabetes development. In this study, we demonstrated that human islets treated in vitro with LSF retained β-cell glucose responsiveness and insulin secretion in the presence of multiple proinflammatory cytokines. In addition, LSF treatment in vitro enhanced basal insulin production in β cells, suggesting that LSF can directly improve β-cell function. LSF reduced β-cell apoptosis induced by proinflammatory cytokines by 50%. Importantly, 30% fewer LSF-treated islets were sufficient to achieve insulin independence in a murine islet transplantation model. These results demonstrate the ability of LSF-like compounds to protect and enhance β-cell function, suggesting the potential of using LSF or its analogs in islet transplantation.